Caffeine and related xanthines are the most widely consumed behaviorally-active substances in the world. They are also used clinically as respiratory stimulants, but the biochemical mechanisms that mediate these effects are poorly understood. The current project utilized operant conditioning techniques and a pressure-displacement plethysmograph to characterize the neurochemical basis of caffeine-induced changes in behavior and respiration. Findings obtained and reported this year demonstrated a clear dissociation of drug effects on behavior and respiration during chronic administration of caffeine. Moreover, the identification of specific neurochemical mechanisms as targets in drug development will likely lead to more effective therapeutic agents in the treatment of respiratory dysfunction.